Jung, H. et al. Nat. Commun. 10, 314 (2019).

Inducible Cre variants are widely used tools in the mouse for controlling gene expression in a spatiotemporal manner. Jung et al. report a photoactivatable Flp recombinase (PA-Flp) that can be used as an alternative to or in combination with Cre. The researchers identified a suitable split site within Flp. They then combined the split Flp with the Magnet system, which leads to reconstitution upon blue light illumination. The researchers optimized the tool in cell culture and then applied PA-Flp in the mouse brain to precisely control the expression of a reporter gene. Furthermore, they combined PA-Flp with a Flp-dependent Cre construct to control the expression of a small hairpin RNA targeting a calcium channel in GABAergic neurons in the medial septum. This treatment resulted in increased object-exploration behavior in the mice. Although not yet explored, PA-Flp could be used for further spatial and temporal refinement of Cre-dependent gene expression.